title: Chronic administration of ezetimibe increases active glucagon-like peptide-1 and improves glycemic control and pancreatic beta cell mass in a rat model of type 2 diabetes.
abstract: Ezetimibe is a cholesterol-lowering agent targeting Niemann-Pick C1-like 1, an intestinal cholesterol transporter. Inhibition of intestinal cholesterol absorption with ezetimibe may ameliorate several metabolic disorders including hepatic steatosis and insulin resistance. In this study, we investigated whether chronic ezetimibe treatment improves glycemic control and pancreatic beta cell mass, and alters levels of glucagon-like peptide-1 (GLP-1), an incretin hormone involved in glucose homeostasis. Male LETO and OLETF rats were treated with vehicle or ezetimibe (10 mg kg(-1)day(-1)) for 20 weeks via stomach gavage. OLETF rats were diabetic with hyperglycemia and significant decreases in pancreatic size and beta cell mass compared with LETO lean controls. Chronic treatment of OLETF rats with ezetimibe improved glycemic control during oral glucose tolerance test compared with OLETF controls. Moreover, ezetimibe treatment rescued the reduced pancreatic size and beta cell mass in OLETF rats. Interestingly, ezetimibe significantly decreased serum dipeptidyl peptidase-4 activity and increased serum active GLP-1 in OLETF rats without altering serum total GLP-1. These findings demonstrated that chronic administration of ezetimibe improves glycemic control and pancreatic beta cell mass, and increases serum active GLP-1 levels, suggesting possible involvement of GLP-1 in the ezetimibe-mediated beneficial effects on glycemic control.
authors.affiliation: Diabetes Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Yang
authors.forename: Jung Mook
authors.initials: JM
authors.lastname: Choi
authors.forename: Lisa
authors.initials: L
authors.lastname: Kim
authors.forename: Byung-Joon
authors.initials: BJ
authors.lastname: Kim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Sohn
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Kim
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Park
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Rhee
authors.forename: Won Young
authors.initials: WY
authors.lastname: Lee
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Oh
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Kim
authors.forename: Cheol-Young
authors.initials: CY
authors.lastname: Park
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D000069438:Ezetimibe; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D000069438:Ezetimibe